Cryo-EM study of patched in lipid nanodisc suggests a structural basis for its clustering in caveolae

doi:10.1016/j.str.2021.06.004

	Cryo-EM study of patched in lipid nanodisc suggests a structural basis for its clustering in caveolae
	Luo, Yitian1,2 ; Wan, Guoyue 1; Zhang, Xiang 1; Zhou, Xuan 1; Wang, Qiuwen1,2 ; Fan, Jialin 1; Cai, Hongmin 1; Ma, Liya 1; Wu, Hailong 1; Qu, Qianhui 3; Cong, Yao 1; Zhao, Yun1,2,4 ; Li, Dianfan 1
	2021-11-04
发表期刊	STRUCTURE (IF:4.4[JCR-2023],4.3[5-Year])
ISSN	0969-2126
EISSN	1878-4186
卷号	29 期号:11 页码:1286-+
发表状态	正式接收
DOI	10.1016/j.str.2021.06.004
摘要	The 12-transmembrane protein Patched (Ptc1) acts as a suppressor for Hedgehog (Hh) signaling by depleting sterols in the cytoplasmic membrane leaflet that are required for the activation of downstream regulators. The positive modulator Hh inhibits Ptc1's transporter function by binding to Ptc1 and its co-receptors, which are locally concentrated in invaginated microdomains known as caveolae. Here, we reconstitute the mouse Ptc1 into lipid nanodiscs and determine its structure using single-particle cryoelectron microscopy. The structure is overall similar to those in amphipol and detergents but displays various conformational differences in the transmembrane region. Although most particles show monomers, we observe Ptc1 dimers with distinct interaction patterns and different membrane curvatures, some of which are reminiscent of caveolae. We find that an extramembranous hand-shake region rich in hydrophobic and aromatic residues mediates inter-Ptc1 interactions under different membrane curvatures. Our data provide a plausible framework for Ptc1 clustering in the highly curved caveolae.
收录类别	SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS记录号	WOS:000718037100009
出版者	CELL PRESS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/243251
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_赵允组生命科学与技术学院_硕士生
通讯作者	Qu, Qianhui; Cong, Yao; Zhao, Yun; Li, Dianfan
作者单位	1.Chinese Acad Sci, Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci,State Key Lab Mol, Shanghai Inst Biochem & Cell Biol,State Key Lab C, 320 Yueyang Rd, Shanghai 200031, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China; 3.Fudan Univ, Shanghai Stomatol Hosp, Inst Biomed Sci, Dept Syst Biol Med, Shanghai 200032, Peoples R China; 4.Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Luo, Yitian,Wan, Guoyue,Zhang, Xiang,et al. Cryo-EM study of patched in lipid nanodisc suggests a structural basis for its clustering in caveolae[J]. STRUCTURE,2021,29(11):1286-+.
APA	Luo, Yitian.,Wan, Guoyue.,Zhang, Xiang.,Zhou, Xuan.,Wang, Qiuwen.,...&Li, Dianfan.(2021).Cryo-EM study of patched in lipid nanodisc suggests a structural basis for its clustering in caveolae.STRUCTURE,29(11),1286-+.
MLA	Luo, Yitian,et al."Cryo-EM study of patched in lipid nanodisc suggests a structural basis for its clustering in caveolae".STRUCTURE 29.11(2021):1286-+.